ChemGAPP: a tool for chemical genomics analysis and phenotypic profiling

Abstract

Motivation High-throughput chemical genomic screens produce informative datasets, providing valuable insights into unknown gene function on a genome-wide level. However, there is currently no comprehensive analytic package publicly available. We developed ChemGAPP to bridge this gap. ChemGAPP integrates various steps in a streamlined and user-friendly format, including rigorous quality control measures to curate screening data. Results ChemGAPP provides three sub-packages for different chemical-genomic screens: ChemGAPP Big for large-scale screens; ChemGAPP Small, for small-scale screens and ChemGAPP GI for genetic interaction screens. ChemGAPP Big, tested against the E. coli KEIO collection, revealed reliable fitness scores which displayed biologically relevant phenotypes. ChemGAPP Small, demonstrated significant changes in phenotype in a small-scale screen. ChemGAPP GI was benchmarked against three sets of genes with known epistasis types and successfully reproduced each interaction type. Availability ChemGAPP is available at https://github.com/HannahMDoherty/ChemGAPP, as a standalone Python package as well as Streamlit applications. Supplementary information Supplementary data are available at Bioinformatics online.

Reduced peptidoglycan synthesis capacity impairs growth of E. coli at high salt concentration

“…S3). Subsequently, genetic interaction scores were calculated by ChemGAPP GI ( 41 ). The package calculates the fitness ratio of two single mutants (ΔA and ΔB) and the double mutant ΔAΔB compared to the WT strain and then calculates the expected double mutant fitness ratio, comparing it to the observed fitness ratio ( Fig.…”

Bam complex associated proteins inEscherichia coliare functionally linked to peptidoglycan biosynthesis, membrane fluidity and DNA replication

“…Endpoint pictures were taken to quantify colony fitness based on size by the image analysis software Iris [27]. Fitness was scored using the chemical genomics analysis software ChemGAPP Small by comparing the mean colony size for the mutant in each condition to the mean colony size of that mutant in the LB agar condition, which was normalised to a fitness score of 1 [28]. Fitness scores below 1 represent decreased fitness, as a function of colony size compared to growth on LB agar, and scores above 1 indicate increased fitness in that condition.…”

“…A total of 4 replica plates were generated for each stress condition. Fitness of the mutants was then scored and analysed using the ChemGAPP Small software [28]. Mean colony size for the mutant in each condition was compared to the mean colony size of that mutant in the LB agar condition, which was normalised to a fitness score of 1 [28].…”

“…Images were then analysed using the software called IRIS to measure the size, opacity and circularity of each colony on the plates [27]. Fitness of the mutants was then analysed and compared using the software ChemGAPP GI [28].…”